rs571983343
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002609.4(PDGFRB):c.2464-3C>T variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0000229 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002609.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDGFRB | NM_002609.4 | c.2464-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261799.9 | |||
PDGFRB | NM_001355016.2 | c.2272-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
PDGFRB | NM_001355017.2 | c.1981-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDGFRB | ENST00000261799.9 | c.2464-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002609.4 | P1 | |||
PDGFRB | ENST00000520579.5 | c.*1778-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | |||||
PDGFRB | ENST00000519575.5 | n.378-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 | |||||
PDGFRB | ENST00000521723.1 | n.317-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251402Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135888
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461638Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727162
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74454
ClinVar
Submissions by phenotype
Infantile myofibromatosis;C1866182:Acroosteolysis-keloid-like lesions-premature aging syndrome;C3554321:Basal ganglia calcification, idiopathic, 4;C4225270:Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 25, 2020 | This sequence change falls in intron 17 of the PDGFRB gene. It does not directly change the encoded amino acid sequence of the PDGFRB protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs571983343, ExAC 0.03%). This variant has not been reported in the literature in individuals with PDGFRB-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at